H3K4me3 recognition by the COMPASS complex facilitates the restoration of this histone mark following DNA replication

Abstract

During DNA replication, parental H3-H4 marked by H3K4me3 are transferred almost equally onto leading and lagging strands of DNA replication forks. Mutations in replicative helicase subunit, Mcm2 (Mcm2-3A), and leading strand DNA polymerase subunit, Dpb3 ( dpb3 ∆), result in asymmetric distributions of H3K4me3 at replicating DNA strands immediately following DNA replication. Here, we show that mcm2-3A and dpb3 ∆ mutant cells markedly reduce the asymmetric distribution of H3K4me3 during cell cycle progression before mitosis. Furthermore, the restoration of a more symmetric distribution of H3K4me3 at replicating DNA strands in these mutant cells is driven by methylating nucleosomes without H3K4me3 by the H3K4 methyltransferase complex, COMPASS. Last, both gene transcription machinery and the binding of parental H3K4me3 by Spp1 subunit of the COMPASS complex help recruit the enzyme to chromatin for the restoration of the H3K4me3-marked state following DNA replication, shedding light on inheritance of this mark following DNA replication.